Method of controlled drug release from a liposome carrier

Abstract

Disclosed are methods and compositions for the controlled release of a drug or agent from a liposome using light or radiation. Also disclosed are compositions comprising liposomes having a lipid layer, wherein the liposomes contain an agent, an enzyme capable of releasing the agent from the liposome, and an enzyme activator sequestered by a molecular cage. In another aspect, methods of delivering an agent to a target in a subject are disclosed.

We claim: 
     
       1. A composition comprising a liposome having a lipid bi layer, the liposome containing
 a) an agent; 
 b) phospholipase A2 or phospholipase C capable of releasing the agent from the liposome when in the presence of a calcium co-factor; and 
 c) a DM-Nitrophen sequestering the calcium co-factor capable of activating the phospholipase, wherein the calcium co-factor is required for activating the lipase. 
 
     
     
       2. The composition of  claim 1 , wherein the molecular cage is photolabile. 
     
     
       3. The composition of  claim 1  wherein the phospholipase A2 or phospholipase C is capable of hydrolyzing at least one lipid in the liposome. 
     
     
       4. The composition of  claim 1 , wherein the agent comprises a chemotherapeutic agent, a polypeptide, a toxin, a radiotherapeutic agent, a radiosensitizing agent, an imaging agent or combinations thereof. 
     
     
       5. The composition of  claim 1 , wherein the liposome further comprises a targeting molecule. 
     
     
       6. The composition of  claim 1 , wherein the liposome further comprises at least one polypeptide capable of localizing to the lipid layer and a protease. 
     
     
       7. The composition of  claim 1 , further comprising a nano-scintillator capable of emitting UV light upon excitation. 
     
     
       8. The composition of  claim 7 , wherein the nano-scintillator is responsive to radiation. 
     
     
       9. The composition of  claim 8 , wherein the nano-scintillator is responsive to X-radiation. 
     
     
       10. A method of delivering an agent to a target in a subject, the method comprising:
 a) administering the liposome of  claim 1  to the subject; and 
 b) exposing the target to light, whereby the light releases the calcium co-factor from DM-Nitrophen, the co-factor activates phospholipase A2 or phospholipase C and phospholipase A2 or phospholipase C releases the agent from the liposome. 
 
     
     
       11. A method of delivering an agent to a target in a subject, the method comprising:
 a) administering the liposome of  claim 7  to the subject; and 
 b) exposing the target to radiation, whereby the radiation activates the nano-scintillator to emit UV light which releases the calcium co-factor DM-Nitrophen, the calcium co-factor activates phospholipase A2 or phospholipase C and phospholipase A2 or phospholipase C releases the agent from the liposome. 
 
     
     
       12. The method of  claim 10 , wherein the target comprises a tumor. 
     
     
       13. The method of  claim 10 , wherein the liposome is administered to a patient before exposing the target to light. 
     
     
       14. The method of  claim 11 , wherein the liposome is administered to a patient before exposing the target to radiation. 
     
     
       15. A method of controlled drug release, the method comprising the method of  claim 10 , wherein the agent is released in a localized area. 
     
     
       16. A method of treating a condition responsive to the agent, the method comprising administering the liposome of  claim 1 . 
     
     
       17. The method of  claim 16 , wherein the condition is cancer. 
     
     
       18. The method of  claim 11 , wherein the target comprises a tumor. 
     
     
       19. A method of controlled drug release, the method comprising the method of  claim 11 , wherein the agent is released in a localized area.